This is a revised submission of a FIRST Award. Bone mineral density (BMD) in later life is attributed to peak BMD attained in early adulthood and both menopause and age-related bone loss. There is compelling evidence to suggest that BMD and its subsequent loss are determined by a combination of genetic and environmental factors. The primary objective of this study is to gain a more comprehensive understanding of genetic and gene-environment interactions as correlates and determinants of BMD in a cohort of 535 healthy women (aged 44-50 years) enrolled in the NIH-funded Women's Healthy Lifestyle Project (WHLP; HL45167; Drs. Kuller and Wing, co-principal investigators). The study proposed will add two candidate genes for osteoporosis, the type I collagen gene and the estrogen receptor gene, using DNA isolated from the baseline examination. The second aim of this application is to examine the effect of a Lifestyle-Intervention aimed at weight loss across the menopause on BMD. The investigators will determine whether differences in BMD between Assessment and Intervention Groups can be explained by differences in markers of bone turnover, including serum osteocalcin and urinary N-telopeptides. They state that this epidemiological study can improve our understanding of the individual variations in BMD and changes in BMD during the critical menopausal years, and the degree to which these differences are mediated by gene-environment interactions. They further state that gaining insight into these mechanisms has important implications for effective prevention and more efficient identification of those individuals at the greatest risk of osteoporosis.